Résumé
Aromatic Amino Acid Decarboxylase (AADC) deficiency is a rare disease caused by pathogenic variants of the dopa decarboxylase gene, resulting in decreased synthesis of dopamine, serotonin and catecholamine. The clinical spectrum includes early developmental arrest, hypotonia, oculogyric crises, dysautonomic features, mood and sleep disorders. Treatments primarily address symptoms and offer modest efficacy. Intracerebral gene therapy, aimed at restoring AADC synthesis, holds promise as a pivotal treatment within the presently limited therapeutic options. The procedure involve bilateral convective stereotactic intraputaminal injection of viral vectors expressing the gene for AADC synthesis (eladocagene exuparvovec, 1.8x1,011 vector genomes, infusion volume of 2x80 microliters per putamen). Immediate post-operative MRI assessments are performed using T1, T2 and Flair sequences to measure deposit volumetrics. Clinical, biological, MRI and PET-DOPA follow-up is scheduled. Six patients, aged between 2.5 and 19 were treated, with follow-ups ranging from 0.5 to 3.6 years. All showed improvement in oculogyric crises between 1 and 6 months, 3 were no longer affected. Improvements in axial tone, motor functions, behavior and sleep were observed. One patient was able to walk with assistance at 32 months. Transient dyskinesias appeared 3-4 weeks after surgery. Deposit volumetrics showed no correlation with clinicobiological results. Intraputaminal gene therapy in AADC deficiency is safe and shows remarkable clinical results across the entire clinical spectrum. Targets, technical modalities and the contribution of imaging remain to be clarified.